Radiation damage to a three-dimensional hydrogel model of the brain perivascular niche

Abstract

Glioblastoma (GBM) is a highly aggressive and recurrent brain cancer characterized by diffuse metastasis at the tumor margins. Radiation therapy is a standard component of current treatment and offers potential for improved patient outcomes. While radiation therapy targets GBM cells in the tumor margins, it may also significantly damage adjacent non-cancerous tissues, leading to reduced quality of life and potentially creating a tumor-supportive microenvironment. The perivascular niche (PVN) in the tumor margins is believed to play a significant role in regulating the glioblastoma stem cell subpopulation as well as serving as a site for cancer recurrence and migration. Understanding the impact of radiation on the PVN can better inform radiation schemes and improve our understanding of GBM recurrence, but is difficult in vivo. Here we adapt a previously developed three-dimensional hydrogel model of the brain perivascular niche to investigate the impact of radiation dosage and delivery rate on perivascular niche properties in vitro. Effects of radiation on vessel architecture can be measured in this hydrogel-based model, suggesting an approach that can provide insight into the effects of radiation on a shorter time scale relative to in vivo experiments. IMPACT STATEMENTGlioblastoma (GBM) is a highly aggressive and recurrent brain cancer characterized by diffuse metastasis at the tumor margins. The perivascular niche (PVN) in the tumor margins plays a significant role in GBM progression and is a target for radiation therapy. We report a method to use three-dimensional hydrogel models of the brain perivascular niche to benchmark the impact of radiation dosage and delivery rate on perivascular niche properties in vitro. This approach provides new insight into the effects of radiation on a shorter time scale relative to in vivo experiments.